We plan to study three major areas: the proteins carried to the synapse by axoplasmic transport, particularly the fast phase of transport; the action of drugs upon axoplasmic transport, with emphasis upon psychoactive agents such as the hallucinogens; and the mechanism of acetylcholine release. The proteins moved by axoplasmic transport are believed to maintain and replenish the axon cylinder, and to supply essential enzymes and other molecules to the synapse itself. The transported proteins must also be active in control of synaptic function. Certain of the proteins transported have been identified, and we will now proceed with the isolation and characterization of these. We have found that different proteins are transported in different nerves. Proteins identified in this way can be correlated with the different functions carried out by the nerves involved. We shall also attempt to detect the proteins responsible for transducing chemical energy into mechanical movement in the transport process. Drugs of several types inhibit the transport of radioactively labelled proteins. We propose to use methods developed in our laboratory to study further the inhibition produced by certain hallucinogens such as mescaline. The time during which the drugs are active will be measured, as will the effects of related compounds. The mechanism of release of acetylcholine (ACh) is being studied with the isolated rat superior cervical ganglion. We have found that the venom of black widow spiders stimulates release of ACH in a manner which mimics, in some ways, the release elicited by electrical stimulation. We shall further characterize this process, planning to purify the specific toxin and use it as an affinity label with which to study the release process.